(1) Summary of the Invention
The present invention relates to a method for detecting drug metabolites which are transferred from a mother to a newborn infant during pregnancy. In particular, the method involves the isolation of meconium from a newborn infant, separation of the drug metabolites from the meconium in solution and assaying for the metabolites in the solution.
(2) Prior Art
The use of illicit drugs in the United States is widespread. According to a national survey in 1985, an estimated 23 million people were users of illicit drugs (1985 National Health Household Survey on Drug Abuse. Rockville, Md., 1987). Although exact figures are not known, a sizeable portion of drug users are women of childbearing age or are pregnant women. Infants born to these drug dependent women have multiple problems. In the neonatal period, their mortality rate is increased as well as morbidity, which includes asphyxia, prematurity, low birth weight, hyaline membrane disease, infections, aspiration pneumonia, congenital malformations, abnormal heart rate and breathing patterns and drug withdrawal (Ostrea E. M, Chavez C. J., Perinatal problems (excluding neonatal withdrawal) in maternal drug addiction: A study of 830 cases J. Pediatr 94:292-295 (1979); Zelson C, Rubio E, and Wasserman E., Pediatrics 48:178 (1971)). Long term sequelae are not uncommon and include delays in physical growth and mental development, sudden infant death syndrome, hyperactivity, ocular and neurologic abnormalities and lately, a risk to acquired immunodeficiency disease (Wilson, G. S., M. McCreary, J. Kean and J. Baxter, Pediatrics 63:135-144 (1979; Chavez, C. J., et al, J. Pediatrics 95:407-409 (1979); Chasnoff, I., J., et al, Pediatrics 70:210-213 (1982); Chavez, C. J., et al., Pediatr Res 12:367A (1979); and Oleske J., et al., J. Am. Med Assoc. 249:2345-2349 (1983)). At present, cocaine abuse among pregnant women has also become widesdpread and infant morbidity, notably cerebrovascular problems have been reported (Chasnoff, I. J., et al., J. Pediatr 108:456-459 (1986)). Because of these immediate and long term problems, infants of drug dependent women (IDDM) constitute a high risk group and have to be identified as soon as possible after birth if intervention is to be successful.
Unfortunately, such detection is not easy. Many of the drugs which the fetus was exposed to in utero, do not produce immediate or recognizable effects in the infant after birth which arouse suspicion (Kandall, S. R., Am. J. Dis Child 127:58-61 (1974)). Maternal admission of drug usage may not always be obtained because of fear of the consequences associated with such admittal. Even with maternal cooperation, the experience has been that the information volunteered by the mother regarding the type and frequency of her drug usage can be inaccurate (Ostrea, E. M., et al., J. Pediatr 88:642-645 (1976)). Lastly, the infant's urine is routinely screened for drugs; however, there is a high rate of false negative results with this method (Halstead, A. C., et al., Clin. Biochem. 21:59-61 (1988).
A previous study showed that the metabolites of morphine were found in high concentrations in the gstlointestines of the fetuses of morphine addicted monkeys (Ostrea, E. M., et al., Dev. Pharmacol. Ther., 1:163-170 (1980)). It was not appreciated that this result would serve as a basis for tests in humans for such drugs.